Polybrominated
diphenyl ether (
PBDE)
flame retardants have become widespread environmental contaminants. The highest body burden has been found in toddlers and infants, due to their exposure through breast milk and
house dust, and the current concern for potential adverse health effects of
PBDEs relates to their developmental neurotoxicity. The mechanisms underlying the neurotoxicity of
PBDEs are largely not understood, though there is evidence that
PBDEs may elicit oxidative stress. In this study, two different mathematical models were used to evaluate the interaction between
BDE-47 and
BDE-99 on viability of neuronal cells. The combined exposure to these compounds induced synergistic effects at concentrations of
BDE-47 below its threshold doses, and in a wide range of
BDE-99 concentrations below its IC(50). In contrast, at concentrations of
BDE-47 near its IC(50) value, and in a wide range of
BDE-99 concentrations, antagonistic effects were observed. The interactions observed on cell viability were confirmed by an assessment of induction of oxidative stress. The finding that co-exposure to
BDE-47 and
BDE-99 could induce synergistic neurotoxic effects, in particular at low doses of
BDE-47, is of much toxicological interest, as humans are exposed to mixtures of
PBDEs, most notably tetra- and
penta-BDE congeners.